Title:Chromosomal rearrangements as barriers to genetic homogenization between archaic and modern humans

Abstract: Chromosomal rearrangements, which shuffle DNA throughout the genome, are an
important source of divergence across taxa. Using a paired-end read approach
with Illumina sequence data for archaic humans, I identify changes in genome
structure that occurred recently in human evolution. Hundreds of rearrangements
indicate genomic trafficking between the sex chromosomes and autosomes, raising
the possibility of sex-specific changes. Additionally, genes adjacent to genome
structure changes in Neanderthals are associated with testis-specific
expression, consistent with evolutionary theory that new genes commonly form
with expression in the testes. I identify one case of new-gene creation through
transposition from the Y chromosome to chromosome 10 that combines the 5' end
of the testis-specific gene Fank1 with previously untranscribed sequence. This
new transcript experienced copy number expansion in archaic genomes, indicating
rapid genomic change. Among rearrangements identified in Neanderthals, 13% are
transposition of selfish genetic elements, while 32% appear to be ectopic
exchange between repeats. In Denisovan, the pattern is similar but numbers are
significantly higher with 18% of rearrangements reflecting transposition and
40% ectopic exchange between distantly related repeats. There is an excess of
divergent rearrangements relative to polymorphism in Denisovan, which might
result from non-uniform rates of mutation, possibly reflecting a burst of TE
activity in the lineage that led to Denisovan. Finally, loci containing genome
structure changes show diminished rates of introgression from Neanderthals into
modern humans, consistent with the hypothesis that rearrangements serve as
barriers to gene flow during hybridization. Together, these results suggest
that this previously unidentified source of genomic variation has important
biological consequences in human evolution.